The long term objective of this project is to advance our understanding of self-tolerance and autoimmunity, emlpoying experimental allergic encephalomyelitis (EAE) in Lewis rats as a model. The specific aims are as follows: 1. To ascertain how autoreactive cells can be activated in vivo to elicit autoimmune disease. We will use recipients of myelin- basic protein (BP) cultured spleen cells (SpC) from nonimmune donors for these studies. These recipients are "primed for EAE but do not develop the disease. We will ascertain whether additional "signals" (provided by adjuvant, antigen, or lymphokines) trigger these cells to induce EAE. 2. To study the cellular interactions which lead to EAE, relying on the use of monoclonal antibodies of known specificity and lymphokines (e.g., interleukin 2) in vitro to inhibit or augment the activation of the effector T cells which induce EAE. The therapeutic value of the monclonal antibodies will be explored. This has potential clinical relevance with respect to MS. 3. To confirm and extend our preliminary finding that suppressor cells which appear after recovery from EAE function via the inhibition of gamma interferon production by EAE effector cells. 4. To develop the chronic relapsing EAE (CREAE) model in the Lewis rat, study suppressor and effector cell function, and determine the role of different central nervous system antigens in this form of the disease. This may provide insight into the pathogenesis of MS.